Circulation and Perfusion Enhancement
Circulation of blood throughout the body and perfusion of end organs are basic functions in humans and most other animals. Many different problems and conditions result when this circulation is altered, obstructed, interfered with, or changed. Substantially all of the body is dependent on circulation for delivery of oxygen and nutrients and removal of waste products. If the pressure or flow rate of circulation to a certain organ or region of the body changes, that certain organ or region can experience loss of function, tissue death, or other impairment.
Some of the organs most dependent on optimal circulation are those that process the blood for the benefit of the entire body. For example, the kidneys, liver and spleen remove waste products or unneeded material from the blood. The small intestine transfers nutrients from consumed food to the blood. Changes to the circulation (also called perfusion) of these organs can have ill effects on the entire body.
Parts of the body that do not process blood for the benefit of the body also suffer from poor circulation. Peripheral vascular disease is characterized by poor circulation to the extremities. Symptoms include swelling, numbness, loss of function, pain, and tissue death. In serious cases, the affected limb or extremity can become gangrenous and amputation is required.
Methods for addressing poor circulation or perfusion include medications that increase the contractility of the heart (inotropes), reduce the fluid load on the heart to improve its function (diuretics), or open blood vessels to increase flow (vasodilators). These medications have disadvantages including, but not limited to, deleterious side-effects, habituation, partial effectiveness, or ineffectiveness. For example, inotropes can increase the risk of death. Diuretics and vasodilators interfere with some of the body's natural compensatory mechanisms, indicating their use involves some trade-off. For example, diuretics may reduce fluid load without actually addressing the underlying poor circulation that led to increased fluid load and vasodilators may increase flow but at reduced pressure (adequate perfusion requires adequate flow and pressure).
Mechanical devices are also used to improve circulation. Two classes of such devices are left ventricular assist devices (LVADs) and intra-aortic balloon pumps (IABPs). LVADs are pumps that are surgically implanted in the chest cavity and connected between the left ventricle of the heart and the aorta to augment the heart's output. IABPs are catheter based devices with a large balloon that inflates inside the aorta while the aortic valve is closed (i.e. during diastole) to force blood further into the circulatory system.
These mechanical devices have disadvantages also. LVAD implantation requires major open heart surgery in a well-equipped operating room and has a lengthy recovery period (forty days or more). Total cost for the procedure can range from a few hundred thousand to a million dollars or more. Additionally, serious complications (e.g. stroke or infection) from the procedure are common. IABPs are safer, but usually limited to short-term in-hospital use. In addition, the effectiveness of an IABP is directly related to the size of the balloon and larger balloons can extend past branches off the aorta (e.g. the phrenic, superior mesenteric, celiac, and renal arteries) that supply blood to several key organs. In this case, these organs may see only limited improvement (or even reduction) in circulation.
In addition to the disadvantages described above, medications, VADs, and IABPs provide systemic level circulatory support that is difficult or impossible to adjust in magnitude or limit to or localize in or focus on a particular organ, area, region, or part of the body. Drug therapy takes some time to have significant impact and is not practical for emergency or acute or short term improvement to circulation or perfusion. LVADs are also not practical for emergency or acute or short term improvement to circulation or perfusion due to the expense, invasiveness, planning, and time required for LVAD implantation.
One helpful context in which to judge, without limiting, the advantage of a system for creating specific enhancements to circulation and perfusion over blood pumps delivering non-specific systemic support is in the treatment of shock.
When a person's tissues are starved of oxygen rich blood over time, the person may enter a state of shock. Shock, usually caused by sepsis, hemorrhage, or acute heart failure, causes millions of deaths per year. Over half of shock patients die, usually as a result of multiple organ failure (MOF). The kidneys are at the root of multiple organ failure: poor perfusion of the renal arteries begins a dangerous feedback loop that can lead to damage of numerous organ systems.
For this reason, prevention of end organ failure is most often focused on supporting the kidneys. Traditional treatments include pharmacologic therapies, IV fluid optimization, vasopressors, and eventually renal replacement therapy (e.g. dialysis). Current therapeutic guidelines have not changed in decades, despite the fact that no pharmacologic treatment has been proven effective in clinical trials and excessive IV fluid burden can cause peripheral and pulmonary edema. Furthermore, the use of pressors to increase blood flow to the kidneys can cause acute and permanent ischemic damage to extremities and other organs.
Mechanical cardiovascular or circulatory support (MCS) to increase blood flow and pressure to the kidneys and/or other end organs is a novel approach to the treatment of shock. Current MCS treatment devices or methods are generally targeted at supporting the coronary vasculature during acute periods of cardiogenic shock, such as following a myocardial infarction or during percutaneous coronary intervention. Among these current approaches, a device that can be configured, without limitation, to deliver specific enhancements in circulation and perfusion, e.g., to improve renal clearance, would be an indispensable tool for cardiovascular or circulatory support.
The systems and methods discussed herein provide cardiovascular support, configurable flow and pressure management, and selective perfusion of specific targeted vessel(s) and end organ(s). Non-limiting examples of uses may include increasing renal perfusion to treat acute/chronic kidney injury; treating cardiogenic, septic, hypovolemic, or hemorrhagic shock; changing carotid perfusion to avoid ischemic stroke or balance the effect of downstream pumps; changing celiac/mesenteric perfusion to treat obesity or bowel ischemia; increasing liver perfusion to treat liver disease; improving perfusion of the heart itself by pulling blood from the coronary sinus, pushing blood into the coronary sinus, or pushing blood into the coronary arteries; and/or diverting flow away from sources of bleeding.